Methods for identifying molecules that modulate lipid binding sites of ion channels

A method for identifying molecules that selectively bind to a lipid binding site of a native integral membrane bound protein, includes (i) providing a solubilized integral membrane protein in a detergent micelle and having a native folding conformation; (ii) providing a soluble lipid analog that binds to the integral membrane protein at the native lipid binding site and causes a change in fluorescence of a fluorophore when bound as compared to unbound; and (iii) screening the solubilized integral membrane protein for binding to a plurality of compounds.